This is a scientific review, published to inform health care professionals and public officials, and for an open peer review. It is not medical advice.
Abstract
Hydroxycholoroquine (HCQ) is effective against COVID-19 in a variety of roles – the main two being antiviral and immunomodulator. This “silver bullet” effect may have caused confusion between different effects. It is better to start HCQ-based treatment as early as possible.
Introduction
Hydroxycholoroquine (HCQ) has many mechanisms against COVID-19. This diversity of mechanisms may have created confusion, even among medical professionals. Most importantly, HCQ and its combinations are effective antivirals against SARS-CoV-2, the coronavirus causing COVID-19. As all antivirals, HCQ combinations should be taken early, before the virus overwhelms the body. Therefore, and because current COVID-19 tests have a large rate of false negatives, Dr. Zelenko recommends starting an HCQ-based treatment immediately upon suspicion of COVID-19 [1]: “Given the urgency of the situation, I recommend initiating treatment based on clinical suspicion as soon as possible, even without confirmatory testing.”
I can understand the theoretical basis for starting immediately. If common flu is treated with antivirals, the CDC recommends starting within 48 hours of symptoms onset [2]: “treatment is most effective when given as early as possible after symptoms develop, and its effectiveness diminishes markedly after 48 hours.” Those antivirals, like oseltamivir, begin acting immediately upon entering the bloodstream [3]. HCQ, however, is different. It needs to accumulate in the tissues, and that takes time. Thus, there seems to be no 48 hours window. HCQ’s anti-viral effect diminishes with every day that treatment is delayed.
HCQ as anti-viral
HCQ+AZ
The most tested HCQ-based treatment for COVID-19 is HCQ+AZ (Azithromycin). This drug combination treatment is associated with Didier Raoult, head of the Institut Hospitalo-Universitaire Méditerranée Infection (IHU) [4], [5]. He and his colleagues cited earlier experience of doctors in China.
The two drugs, HCQ+AZ, are considered synergetic in suppressing the SARS-CoV-2 spike — ACE2 interaction, which the coronavirus uses to enter the cell [5], [6]. These “spikes” make up the crown, or “corona”, which gives this type of virus its name. AZ is also an antibiotic, necessary to protect the body from any opportunistic bacterial infection during treatment.
To suppress the SARS-CoV-2 spike – ACE2 interaction, HCQ must accumulate in the lungs. This process begins when HCQ enters the bloodstream and proceeds slowly from there. This is explained in [7] (on chloroquine):
Drug disposition proceeds in three phases—distribution from blood to tissues, equilibration between blood and tissues, and release from tissues back into blood. These phases have half-lives of 3–8, 40–216 h, and 30–60 days, respectively
The times vary by tissue.
HCQ+Zn+antibiotic
Zinc (Zn) prevents viruses from multiplying within cells, however, little Zn is found within cells. Zn ions cannot cross cell membranes. HCQ is known as Zn ionophore – it crosses cell membranes and carries Zinc with it [8]. This antiviral mechanism is entirely distinct from HCQ+AZ ability to suppress the SARS-CoV-2 spike – ACE2 interaction.
Unfortunately, HCQ does not shuttle back and forth through cell membranes carrying Zn but tends to enter the cells and stay there. Some level of tissue saturation is needed for HCQ to be effective as an ionophore.
I am not aware of any reported results on HCQ + Zn + (non-AZ antibiotic) treatment for COVID-19. Dr. Vladimir Zelenko and Dr. Anthony Cardillo (Thousand Oaks, CA) give their patients HCQ + Zn + AZ, so it is hard to say whether HCQ + Zn works. Dr. Zelenko has just registered a clinical trial [9], in which he will compare HCQ + Zn + AZ vs. HCQ + Zn + Doxycycline. Doxycycline is a milder antibiotic with no known activity against the coronavirus.
HCQ
When used on its own, HCQ does exhibit antiviral effect against COVID-19, but not strong enough [10].
HCQ as an Immunosuppressant
HCQ is most known as an immunomodulator (mild immunosuppressant). Hence, its use against auto-immune diseases like lupus and rheumatoid arthritis. The main direct cause of death from COVID-19, like many other pulmonary diseases, is a cytokinetic storm and related acute respiratory distress syndrome (ADRS). This is caused by excessive immune reaction to the infection, which leads to multiple organ failure and death. HCQ decreases this excessive reaction and can do so at any time in the development of COVID-19. Apparently, early attempts to use HCQ against COVID-19 were done in the late stages of the disease.
Remarks
HCQ combinations are being used for COVID-19 treatment all over the world, from India to Czechia, with excellent results. Random population sampling is needed to evaluate the spread of the coronavirus infection and immunity to it.
Chloroquine was noticed for its antiviral and immunomodulatory effects in context of SARS epidemic in 2003 [11]:
Chloroquine exerts direct antiviral effects, inhibiting pH-dependent steps of the replication of several viruses including members of the flaviviruses, retroviruses, and coronaviruses.
… chloroquine has immunomodulatory effects … which mediate the inflammatory complications of several viral diseases.
… the tolerability, low cost, and immunomodulatory properties of chloroquine/hydroxychloroquine are associated with biochemical effects that suggest a potential use in viral infections, some of whose symptoms may result from the inflammatory response.
As regards viral diseases, what is clear is that the drug has antiviral and immunomodulatory effects that warrant particular consideration.
References
| [1] | V. Zelenko, “To all medical professionals around the world,” 2020. |
| [2] | Centers for Disease Control and Prevention (CDC), “What are Flu Antiviral Drugs,” 2019. |
| [3] | B. Davies, “Article Navigation Pharmacokinetics of oseltamivir: an oral antiviral for the treatment and prophylaxis of influenza in diverse populations,” Journal of Antimicrobial Chemotherapy, 2010. |
| [4] | P. Gautret and D. e. a. Raoult, “Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: A pilot observational study,” Travel Medicine and Infectious Disease, 4 April 2020. |
| [5] | G. Hache and D. e. a. Raoult, “Combination of hydroxychloroquine plus azithromycin as potential treatment for COVID 19 patients: pharmacology, safety profile, drug interactions and management of toxicity.,” Mediterranee Infection, 22 April 2020. |
| [6] | G. Sakoulas, “ACE2 Is the SARS-CoV-2 Receptor Required for Cell Entry,” NEJM Journal Watch, 18 March 2020. |
| [7] | D. J. Browning, “Pharmacology of Chloroquine and Hydroxychloroquine,” in Hydroxychloroquine and Chloroquine Retinopathy, Springer, 2014. |
| [8] | J. e. a. Xue, “Chloroquine Is a Zinc Ionophore,” PLOS ONE, 2014. |
| [9] | A. Thakore, “Hydroxychloroquine and Zinc With Either Azithromycin or Doxycycline for Treatment of COVID-19 in Outpatient Setting,” clinicaltrials.gov, 1 May 2020. |
| [10] | C. e. a. A. Devaux, “New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19?,” International Journal of Antimicrobial Agents, 12 March 2020. |
| [11] | A. Savarino and et al., “Effects of chloroquine on viral infections: an old drug against today’s diseases,” The Lancet, November 2003. |
In UK my NHS GP practice now offer HCQ treatment at an early stage, if you have temperature and a cough you are prescribed it! Apparently this is what GP are being told to do.
You have to register with a central NHS website as they are keeping track of what happens.
Thanks, John. Interesting information. Can you say approx where is your GP practice based? Did you ask them, or did they circulate this info to you?
A number of talking points….
VitD3 is a proven stimulus for the immune system and dark skinned people are lacking this essential vitamin when they live in the far northern hemisphere also obese people tend to store VitD3 in the fat so it is less effective…now check which patients have worse outcomes ref Covid19.
Hydrochloroquine basically allows zinc into the cells to prevent Covid reproduction so for any significant results zinc is necessary as a supplement as well.
Since we are not allowed to buy Hydrochloroquine it is possible to buy Quercetin which also allows zinc to penetrate the cells….with no side effects at all!
So, to protect yourself take 4000iu Vit D3 daily to improve the immune system and at the first sign of Covid symptoms take 500+mg Quercetin and 50 mg Zinc daily.
You can find more details of this on line.
Reopening Updates: All 50 States and District of Columbia
https://www.theepochtimes.com/reopening-updates-all-50-states-and-district-of-columbia_3338971.html
I’m surprised nobody has referred to the EVMS covid protocol, which is the result of front-line experience treating covid. The most important takeaway is early and aggressive treatment using easily available meds.
The following is the latest version, it is worth reading in full:
https://www.evms.edu/media/evms_public/departments/internal_medicine/EVMS_Critical_Care_COVID-19_Protocol.pdf
Terry has mentioned it frequently. It would be helpful if that document was in another form than pdf.
Here a an article on it. There seems to be reluctance on this site to real cover it
https://spectator.org/a-report-from-the-front/
Give it time. This is a subject that most people are not comfortable with at all, and prefer to follow the crowd. That link you provided is good.
This is the first time I’ve seen “terry” mention anything.
Been posting something on here every day
Hare to get thru the chaff
Been requesting top level article
Virol J. 2005; 2: 69.
Published online 2005 Aug 22. doi: 10.1186/1743-422X-2-69
PMCID: PMC1232869
PMID: 16115318
Chloroquine is a potent inhibitor of SARS coronavirus infection and spread
Martin J Vincent,1 Eric Bergeron,2 Suzanne Benjannet,2 Bobbie R Erickson,1 Pierre E Rollin,1 Thomas G Ksiazek,1 Nabil G Seidah,2 and Stuart T Nicholcorresponding author1
Author information Article notes Copyright and License information Disclaimer
Conclusion
Chloroquine is effective in preventing the spread of SARS CoV in cell culture. Favorable inhibition of virus spread was observed when the cells were either treated with chloroquine prior to or after SARS CoV infection. In addition, the indirect immunofluorescence assay described herein represents a simple and rapid method for screening SARS-CoV antiviral compounds.
There is no viability data for the cells. No bright field picture.
Untreated cells have a distinct separation of cytoplasm vs. nucleus, CQ-treated cells are balled up which is an indicator of toxicity.
What makes the paper even more dubious is the picture duplication between Fig1 und Fig2. The picture for the untreated cells is the same.
The stock price for Gilead, the patent holder of remdesivir, has gone from $63.20 on Jan 31 to a high of $83.99 on April 17. It has since leveled off in the $80 range.
Any questions?
Just an aside concerning Doxycycline. It was mentioned briefly in the article as a milder antibiotic. I was on a long term course of doxy, 200 mg per day, but stopped because one of the side effects is a mild dry cough. Since a dry cough is now stigmatic, the reaction of people nearby is fear. I also wanted to be sure any cough might be a sign of something else rather than a side effect of the doxy. I will resume the treatment when the time is right.
Here are the COVID-19 cases and deaths of France and Turkey. Turkey gives HCQ at the onset of symptoms. France does not.
https://twitter.com/Covid19Crusher/status/1257921469914517505/photo/1
Here are the total cases and deaths in Morocco. Morocco started giving HCQ at onset April 8th. Notice a change in the graph?
https://twitter.com/Covid19Crusher/status/1257986586999996419/photo/1
We can put together a package of a 6-10 day course of HCQ/Zn and give them to anyone who has symptoms as early as possible. The drugs are extremely safe and cheap. If given early it shortens the time of infection and transmittal.
Here’s a study on something that I’ve been convinced from the beginning is a significant factor in disease progression: glutathione deficiency. Glutathione is the primary antioxidant in the epithelial lining fluid of the lower respiratory tract (where coronavirus does its damage), that protects against pathogens, pollutants and reactive oxygen species (ROS).
Coronavirus infection causes increased ROS in the lungs by decreasing ACE2’s anti-inflammatory counter-regulation of ACE. There’s a medcram video explaining this.
ROS degrades hyaluronan (HA, a high molecular weight polymer that forms a gel to protect the lungs) into smaller pieces that cause inflammation and possibly cause the hyaline membrane formation seen in covid patient chest x-rays and CT. Autopsies have revealed over-accumulations of a gel like substance in patients’ lungs that may be HA.
I have suspicion that HA may be responsible for the unusual hypoxemia (low O2) with hypocapnia (low CO2) seen in covid patients. I would love to know the gas diffusion properties of HA in comparison to the proteinaceous and fibrotic materials in ARDS and pneumonia patients, who have hypoxemia and hypercapnia (high CO2). CO2 is 20x more diffusable than O2 in the lungs. Do covid patients have silent hypoxemia (low O2/CO2) because HA hinders O2 diffusion while allowing CO2 diffusion? Whereas the proteinaceous and fibrotic materials in ARDS and pneumonia patients’ lungs hinder diffusion of both?
N-acetylcysteine (NAC) supplement increases glutathione levels (glutathione precursors are cysteine, glycine, and glutamine), but glutathione supplements don’t work so well. Hospitals often use NAC as standard treatment, but they also use other things that deplete glutathione like acetaminophen (paracetamol) and anti-viral drugs.
Endogenous deficiency of glutathione as the most likely cause of serious manifestations and death from novel coronavirus infection (COVID-19): a hypothesis based on literature data and own observations
https://www.researchgate.net/publication/340917045_Endogenous_deficiency_of_glutathione_as_the_most_likely_cause_of_serious_manifestations_and_death_from_novel_coronavirus_infection_COVID-19_a_hypothesis_based_on_literature_data_and_own_observations
A little research on glutathione reveals that it is naturally produced by the body, but that production decreases with age. Environmental pollution also lowers the level of glutathione in the body.
A correlation with COVID-19 and more severe cases affecting the older population and those living in crowed cities with even slight levels of air pollution may to be real if glutathione deficiency is indeed a factor.
Basically, any kind of oxidative stress depletes glutathione (GSH). One study I read found that alcohol abusers’ lungs had 80-90% less GSH than normally found in healthy lungs. Alcohol damages the liver where GSH is synthesized, plus it consumes GSH as it is detoxified. Alcohol abusers are prone to get a pneumonia condition called alcoholic lung. They say the cause is unknown, but I suspect that it’s at least partly due to GSH depletion.
Vitamin C is another thing that helps rejuvenate glutathione.
Low Nourishment of Vitamin C Induces Glutathione Depletion and Oxidative Stress in Healthy Young Adults
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4596346/
Hey, thanks for this info.
On the side, one of the many things I do to mitigate an OA knee, I religiously take a liquid HA suppliment (low molecular weight?).
I always worry wether suppliments like this realy are absorbed and do any good.
Comments on this one?
I don’t know anything about HA supplements.
btw I was wrong about HA being high molecular weight. It’s a long chain molecule.
I have found that if you ask the naysayers of the cheap well tested drugs, “what do you think of remdesivir” ? the naysaying turns to approval, it becomes the only drug that effectively saves lives. Now there is a great deal of profit for Gilead and it has been noticeable while the promotion and priming by Gilead has pushed up their share price. Seems to me that “follow the money” may account for paid influencers to permeate sites to put down any cheaper 10c a tablet effective treatment, and it seems the CDC and WHO is also full of active pro big Pharma profit lines.
yep follow the money…
Besides following the money you have to follow the political gain. The virus is viewed as a tool to defeat him by the Deep State. A cure is the LAST thing that they want to see until after the election. In their eyes 10s of thousands of dead is a small price to pay for his defeat.
Is YouTube invested in remdesivir? Would that explain their purge of HCQ videos?
KenB
Generalize much?
One thing you never hear is the health cross sections of those that die in the ICU. Almost all (at least in the west) are obese with hypertension or diabetes (which most obese people have) or are over 70 with hypertension or diabetes.
The obese group is Peter paying the piper where they put themselves at risk. Even the younger people who die are obese. The older group is just a consequence of aging. CV19 gets in a nursing home and wipes out half the population and some of the staff (where a lot fall into the obese category). This also occurs annually with the Flu in nursing homes though certainly not on the scale of CV-19.
So basically out of 100 people getting CV-19, 20 will be symptomless or asymptomatic, 60 will make it through on their own, 20 will go to the hospital, 10 of those will go to the ICU and 5 of those will die. Treating the 80 with symptoms as early as possible matters. It shortens the time for the 60 not going to the hospital and would no doubt increase the odds of getting the 20 going to the hospital either not having to go and if they go, not having to go into ICU. Why people displaying symptoms were told to just stay at home and ride it out is beyond me.
“The obese group is Peter paying the piper where they put themselves at risk.”
Note that being obese is a sign of deeper problems — metabolic syndrome — which does not go well with CV-19.
https://thefatemperor.com/ivor-cummins-dr-aseem-malhotra-dr-campbell-murdoch-viral-update/
I think I heard someone state that 92% of all deaths involved patients with high BMI numbers.
It looks as the Swedish Covid-19 method is not doing too well, currently above USA (21/100k), way up above Germany, and fast catching up with Holland.
http://www.vukcevic.co.uk/EuropeCV.htm
They’re just accumulating their deaths now rather than later this summer. Flattening the curve was never going to reduce the area under the curve. Unless Sweden’s health system is overwhelmed (it’s not) then what’s your point?
brians356-
Exactly the point I have been making to family and friends, since the beginning of the “stay home” orders. Unfortunately with most of them, their eyes just glaze over, and they change the subject.
I think this is the result of the abysmal math education in our public schools. They don’t understand that if the virus’ characteristics don’t change and there is no effective treatment, then it doesn’t matter how much the curve is “flattened,” the area under the curve will be the same. Which means the same number of people will get the virus.
Most people seem to think that “flattening the curve” means that fewer people will get sick and fewer will die. We see this in local and state officials statements about loosening restrictions and opening the economy. They say “okay, we will open up businesses again, but if the number of cases goes up, we’ll have to shut down again.” Absolutely no understanding of how epidemics work. Of course the number of cases will go up. Your comment is perfect : “unless [the] health system is overwhelmed… then what’s your point”?
In summary “The work that we’re doing really adds to the arsenal of agents that could be useful if a resurgence occurs,”
https://www.msn.com/en-au/news/australia/potential-coronavirus-treatment-announced-using-plasma-of-recovered-patients/ar-BB13Fbn4
“Hache, G. & Raoult, D. e. a., 2020. Combination of hydroxychloroquine plus azithromycin as potential treatment for COVID 19 patients: pharmacology, safety profile, drug interactions and management of toxicity.. Mediterranee Infection, 22 April.”
Looked at it. Interesting data about serum concentration of HCQ:
0.46 µg/ml.
MW of HCQ is 335.87 g/mol makes 1.37 µM.
That is some useful information.
Here is the in vitro study that started all the hype:
https://www.ncbi.nlm.nih.gov/pubmed/32020029
They claim their EC90 is 6.90 µM.
That is significantly off from what you get in the serum.
But that is not the issue I have with this and other in vitro studies I found.
1) All the studies are using Vero-6 cells as a model. That is an aneuploid kidney monkey cell line. Not even from a rhesus monkey. People like to use it because it is easily infected but the concentrations used in these cells are not telling you something about the effectiveness and more important anything about toxicity for not immortalized cell lines.
2) The lowest really effective concentration in the studies (MERS, SARS, SARS-CoV-2) in Vero-2 cells is 10 µM (which they used for the western blot). That one is toxic for non-immortalized human cells even for short exposure.
3) From the way the drugs were applied there could be a direct extracellular effect on the virus. Actually, the results point into this direction.
4) Vero-6 cells and a lot of other cell lines are not very efficient to measure replication of the SARS virus:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1075706/
I don’t know how well that translates for SARS-CoV-2 but the study addresses NOT the replication which is THE mode of action people are claiming is affected by Zn2+ and HCQ.
Looked at this reference too:
“J. e. a. Xue, “Chloroquine Is a Zinc Ionophore,” PLOS ONE, 2014.”
The authors used 100 µM of chloroquine. That is ~100x more than the concentration that could be measured in patient’s plasma. This is highly toxic to non-immortalized/non-cancer cell lines.
But there is another issue:
Chloroquine inhibits proton pumps in lysosomes. That is well known. The effect of Zn2+ accumulation in lysosomes could just be through this effect as H+/Zn2+ antiporters are crucial in lysosomal Zn2+ homeostasis.
General impairment of lysosomal function is shown in the paper by accumulation of marker protein LC3B.
This paper below shows that bafilomycin A, a well known very specific proton pump inhibitor for lysosomes, induces Zn2+ accumulation in lysosomes as well:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4095854/
The authors also show that Zn2+ transporters and their inhibition are the mechanism how Zn2+ accumulates in lysosomes. NOT a ionophore funtion.
Another thing caught my eye:
LC3B is also a marker for impaired autophagy.
But other peer-reviewed publications have shown for SARS that the opposite, enhanced autophagy, is beneficial for fighting of the virus. There is indeed a pre-print paper that the same seems to apply to SARS-CoV-2:
https://www.biorxiv.org/content/10.1101/2020.04.15.997254v1
The authors suggest to use niclosamide as a candidate for treatment of SARS-CoV-2.
Conclusion:
The evidence that chloroquine works the way most people here think it does (as a Zn2+ ionophore) is not well supported by direct biological data. There is a high likelihood the reported property to be a Zn2+ ionophore was a misinterpretation of results and insufficient understanding of cellular Zn2+ and lysosomal homeostasis.
The direct data on virus replication is basically non existent and directs more to an impairment of infection but with a chloroquine concentration not achieved in serum.
It might still be there is a possibility a combination of Zn2+/HCQ has beneficial effect through unknown mechanism. But that needs to be determined.
Ron,
In reply to: “The authors used 100 µM of chloroquine. That is ~100x more than the concentration that could be measured in patient’s plasma. This is highly toxic to non-immortalized/non-cancer cell lines.”
This is an in vitro test to determine mechanism not dosage. The Hydroxychloroquine dosage to get the Zinc into our cells is much lower.
And there is field data. There is a doctor in New York that treated 700 patients with a clinically normal dosage of Hydroxychloroquine and only had one death and the death occurred when the person stopped the treatment.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4182877/pdf/pone.0109180.pdf
And this doctor treated 700 covid patients with and had only one death.
This is the Jewish physician that treated 700 sick covid patients with Hydroxychloroquine and Zinc supplements with close to 100% success rate.
https://techstartups.com/2020/04/03/updates-from-dr-vladimir-zelenko-now-treated-700-coronavirus-patients-with-99-9-success-rate-using-hydroxychloroquine-zinc-sulfate-and-z-pak-1-outpatient-died-after-not-following-protocol-exclusi/
@William Howard Astley
“This is an in vitro test to determine mechanism not dosage. The Hydroxychloroquine dosage to get the Zinc into our cells is much lower.”
That is an unproven claim. Where’s the data?
You also missed my point that the data doesn’t even proof that chloroquine is a Zn2+ ionophore. It just corroborates the finding that inhibiting lysosomal protein pumps leads to accumulation of Zn2+ in them. Bafilomycin A or knockdown of ZnT2 or 4 does the same. No ionophore function.
“And this doctor treated 700 covid patients with and had only one death.
This is the Jewish physician that treated 700 sick covid patients with Hydroxychloroquine and Zinc supplements with close to 100% success rate.”
Information from the article is complete meaningless. No age distribution and co-morbidities given.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4182877/
PLoS One. 2014; 9(10): e109180.
Published online 2014 Oct 1. doi: 10.1371/journal.pone.0109180
@Krishna Gans
I was discussing exactly this study above. Here my quote:
“The authors used 100 µM of chloroquine. That is ~100x more than the concentration that could be measured in patient’s plasma. This is highly toxic to non-immortalized/non-cancer cell lines.
But there is another issue:
Chloroquine inhibits proton pumps in lysosomes. That is well known. The effect of Zn2+ accumulation in lysosomes could just be through this effect as H+/Zn2+ antiporters are crucial in lysosomal Zn2+ homeostasis.
General impairment of lysosomal function is shown in the paper by accumulation of marker protein LC3B.
This paper below shows that bafilomycin A, a well known very specific proton pump inhibitor for lysosomes, induces Zn2+ accumulation in lysosomes as well:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4095854/
The authors also show that Zn2+ transporters and their inhibition are the mechanism how Zn2+ accumulates in lysosomes. NOT a ionophore funtion.”
And further:
“The evidence that chloroquine works the way most people here think it does (as a Zn2+ ionophore) is not well supported by direct biological data. There is a high likelihood the reported property to be a Zn2+ ionophore was a misinterpretation of results and insufficient understanding of cellular Zn2+ and lysosomal homeostasis.”
Having a result is one thing, knowing all the possible explanation for it and designing further experiments to clarify which one is the most likely another.
I didn’t see this cited in this thread:
https://www.oann.com/doctors-report-hydroxychloroquine-has-over-90-chance-to-cure-coronavirus-patients/
Here in the interior of BC there are virtually no cases with most of the cases being in Vancouver. Haven’t had this long a period with minimal work as the hospitals are supposed to be emptied in anticipation of the tidal wave of SARS-2 patients who will arrive any time now. My January prediction was that overall health and nutritional status would be determinents of who would do poorly. In many ways, SARS-2 looks very similar to 2009 H1N1 where young people who died in ICU were morbidly obese poorly controlled diabetics. SARS-2 has many different properties, but did find an interesting paper looing at role of Selenium in viral infections. Low Se levels worsen viral infections and I’ve been telling my patients to take 100-200 micrograms of Se daily along with Vitamin D3 2000-5000 units daily (depending on their summer sun exposure), and to have Zinc ready for when they need it.
Zinc has a long history of being used to treat viral infections and I recall Zinc lozenges being widely touted to treat common cold (perhaps it only treats the Corona virus related colds) and many of my patients swore by it but others had no benefit. With Zinc, it’s important to take it 3-4x/day with onset of symptoms and then stop. This would also be when people would start Hydroxychloroquine/Azithromycin.
Another factor that will increase inflammatory response is ratio of omega3/6 fatty acids (w3/w6). US diet is notoriously high in w6 fatty acids and this is associated with high levels of inflammation. w3 fatty acids (found in fish oil) are anti-inflammatory and are converted to resolvins which reduce inflammation produced by pro-inflammatory prostaglandin and other inflammatory mediators produced from w6 fatty acids. I’ve used high dose w3 supplementation in patients with traumatic brain injury to speed up recovery. Morbid obesity is associated with a chronic inflammatory state which is worsened if the same person has diabetes. Unfortunately, the only cure for morbid obesity is to stop eating carbs and go on a high protein, saturated fat diet and exercise which is heresy in the US where saturated fat is considered poison. Some of the far milder effects on population in Japan and Korea are likely due to those populations consuming far more fish and seafood which result in less baseline inflammation.
The one other drug that’s been used in some of the trials I’ve seen is Atorvastatin which lowers cholesterol as a side effect, but primarily modifies cyclo-oxygenase to produce resolvins instead of inflammatory prostaglandins. It’s part of our stroke protocol here and also ASA is added which also modifies cyclo-oxygenases to produce resolvins.
Another factor, which no longer surprises me, is that people who have recieved influenza vaccine are more likely to have a more severe case of SARS-2. I find the US preoccupation with vaccination somewhat puzzling as vaccination associated side effects, when done on a mass scale, often outweigh any potential benefit. When Bill Gates is pushing a coronavirus vaccine I immediately get very suspicious as anyone who came up with a POS like windoze and hopefully his plans to rake in more billions from a very unlikely to be usefull vaccine will meet the same fate as when he claimed that internet explorer was an integral part of the windoze OS around 2000.
There’s also a lot of inter-individual variability with SARS-2 and having time to delve into virology for the last month has been fascinating in terms of how advanced molecular biology has become and the ease with which viral modification can be done with gain of function experiments for some rather nasty virii.
Have handed out packets of hydroxychloroquine and azithromycin to patients I consider at high risk. Interestingly, the center for disease control in BC is strongly cautioning doctors to not use this “experimental treatment” but lots of doctors have stocked up themselves and are using this treatment despite being told they shouldn’t.
Doxycycline was mentioned as a possible antibiotic to use, and was one I was considering as it’s also a metaloprotease inhibitor and for years people have been trying to synthesis a molecule that just keeps metaloprotease inhibition and not antibiotic effect which is bacteriostatic instead of bacteriocidal. 15 years ago I had patients in Vancouver asking me for prescriptions for minocycline for their rheumatoid arthritis as they believed that it was a chronic infection. Did try it on one patient and she had significant reduction in her symptoms and objective signs of improvement; very interesting and it turns out the metaloprotease inhibition resulted in a decrease in inflammation and improvement of symptoms. Told her at the time that it seemed to be working but I didn’t think she had a chronic infection. Have to look at the other systems that every drug affects some of which we don’t know about yet when they’re used.
“Doxycycline … a metaloprotease inhibitor ”
ACE and ACE2 are zinc metalloproteases. Do you think doxycycline inhibits them? There is speculation that ACE inhibitors keep the RAS from swinging too hard towards the ACE/AngII/AT1R inflammatory axis when coronavirus damages the ACE2 anti-inflammatory axis.
That’s a very good question which I can’t answer, but most of the medical literature dealing even remotely with SARS-2 is no longer behind paywalls (I guess that’s one benefit of the lockdown – keeps people like me from going crazy).
Normally I only am concerned with run of the mill ACE receptor and first time I heard about ACE2 was in February when found it was binding site for SARS-2. Have a _lot_ of reading to do in this area to catch up as, clinically, we don’t need to concern ourselves with it. ACE2 seems to be concerned with remodelling of myocardiam and pulmonary arteries (and likely most of the vasculature) and can either raise or lower bp so, for the moment, I know it’s there and have a deeper dive into that area planned when virology has become too confusing/boring. One interesting finding that came out in a single paper was that SARS-2 will infect endothelium of blood vessels and this has been seen in histology of patients who’ve died of SARS-2. Endothelial dysfunction is present in a lot of people with hypertension and I can see ACEI as being detrimental as they’re non-specific protease inhibitors and one of the ways I can tell if someone is septic if their usual bp is poorly controlled and they come in very hypotensive – result of bradykinin and similar small peptides. ARBs don’t have that side effect.
I can’t see any harm in trying Doxycycline as it’s well tolerated and people are on it for months or years for chronic infections or for acne. Someone being on and ACEI might just indicate that they have significant endothelial dysfunction. Nutritional status is huge and, despite my making recommendations to the GP’s that take care of people in extended care about them coming in VitD deficient, the next time they come in to hospital, they’re hypophosphatemic and hypocalcemic with elevated PTH (the rapid way of diagnosing VItD deficience as VitD assays take weeks to come back) and not on VitD. Black population needs much higher doses of VitD given that time is takes for them to produce adequate VitD is proportional to darkness of their skin.
It’s frustrating to not have had any direct contact with SARS-2 patients in hospital as it’s just so rare here in interior of BC. Where I work, no-one has died of SARS-2 in hospital and I suspect that by scaring people away from the hospital there’ll be a huge influx of people once things are back to something close to “normal”. I work in an area where people don’t see a doctor unless absolutely necessary (very refreshing after dealing with the opposite in Vancouver), and they will have been without medical attention for a lot longer than they usually are. OTOH, the overall death rate might have gone down since multiple studies of doctors strikes have shown a decrease in overall death rate which suggests that not tinkering too much with peoples physiology is likely beneficial.
“The center for disease control in BC is strongly cautioning doctors to not use this “experimental treatment”.
Is the logic “no treatment is better than an experimental treatment” compatible with the Hippocratic Oath?
Funny … ‘Clyde’ has not chimed in here with his usual litany of warnings and cautioning those reading and posting to “not be their own prescribing physician”.
Another report I read recently suggested that Zantac and PepcidAC had shown some positive results in treatment of patients with ChiCom-19. To me, this makes some sense, as H2 histamine blockers have been shown to play a role in reducing inflammatory immune reactions.
Here is a new twist to the Wuhan virus, … https://www.youtube.com/watch?v=x2LJy639j8Q
The video is claiming that a virologist has been found murdered, and also talks about leaked govt documents proving that the government knew of human to human transmission early on.
Hi Leo. Have you looked at the correlation of serious covid symptoms and Vitamin D deficiency? 19 times more likely to have serious conditions. Deficient compared to Normal.
Our body has a system to protect it against virus attacks. That explains why many people who have had covid are asymptotic.
Zinc is also the likely natural means our body has to stop viruses from replicating. There is likely natural microbiological system, that requires higher levels of 25(0H)D to activate.
That natural system that gets free Zinc into our cells which has been shown to stop the covid virus from replicating.
The problem that natural system does not work as we are deficient in ‘Vitamin’ D, the prohormone that is used in 200 microbiological processes in the body.
The first line of defense against Covid, should be correcting the Vitamin D deficiency that affects 42% of the UU population.
This study and others show that people who are vitamin D deficient are 19 times more likely to die from covid and have serious complications as compared to people who are Vitamin D ‘normal’, 25(OH)D, 30 ng/ml which requires 4000 UI/day of Vitamin D supplements for most people to achieve.
Patterns of COVID-19 Mortality and Vitamin D: An Indonesian Study
https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3585561
Vitamin D Insufficient Patients 12.55 times more likely to die
Vitamin D Deficient Patients 19.12 times more likely to die
4000 UI/day of Vitamin D supplements is required to raise the serum 25(OH)D above 30 ng/ml.
For Vitamin D status, cases were classified based on their serum 25(OH)D levels:
(1) normal – serum 25(OH)D of > 30 ng/ml,
(2) insufficient – serum 25(OH)D of 21-29 ng/ml, and
(3) deficient – serum 25(OH)D of < 20 ng/ml.
This classification was based on existing literature. 16
https://tahomaclinic.com/Private/Articles4/WellMan/Forrest%202011%20-%20Prevalence%20and%20correlates%20of%20vitamin%20D%20deficiency%20in%20US%20adults.pdf
Prevalence and correlates of vitamin D deficiency in US adults
Mounting evidence suggests that vitamin D deficiency could be linked to several chronic diseases, including cardiovascular disease and cancer. The purpose of this study was to examine the prevalence of vitamin D deficiency and its correlates to test the hypothesis that vitamin D deficiency was common in the US population, especially in certain minority groups.
The overall prevalence rate of vitamin D deficiency was 41.6%, with the highest rate seen in blacks (82.1%), followed by Hispanics (69.2%). Vitamin D deficiency was significantly more common among those who had no college education, were obese, with a poor health status, hypertension, low high-density lipoprotein cholesterol level
This is a chart that shows the diseases (cancers) that have been found to be caused by Vitamin D deficiency.
https://www.grassrootshealth.net/wp-content/uploads/2017/05/disease-incidence-prev-chart-051317.pdf
That last chart is a bit scary; even Tribal East Africans (known to be far less susceptible to ‘modern’ diseases than ‘modern’ man) do not appear to have Vit D levels to be completely out of the woods.
Then again, factor-in a less processed diet, lack of obesity, lifestyle factors, etc and one might anticipate why they tend to be in such rude health compared to us lot.
Another trial claims positive results https://www.randombio.com/cq.html
O
Another observational study[1] came out the other day showing a highly significant effect of chloroquine in reducing the amount of SARS-CoV-2 virus. Details are here.
Virus Kaplan-Meier curve from Huang et al
Virus Kaplan-Meier curve from Huang et al. (2020) [1]
It’s not the randomized placebo-controlled trial we’ve been waiting for, and the study is far from perfect, but their graph shows a highly statistically significant difference in the rate of clearance of the virus (see graph). The subjects were all moderately severely infected with SARS-CoV-2. No deaths were reported.
This is only a few days after another trial from Wuhan Tongji Medical College[2] claiming that moderate doses of hydroxychloroquine produced highly significant reductions in mortality in severely ill COVID-19 patients. Details are here.
Other studies have found no significant effect. What’s going on? Do these drugs work or not? Why is the science so confused? Several possible reasons:
There are now many different strains of SARS-CoV-2 virus. Different sources give different numbers. The number increases daily. Here’s a phylogenetic map.
Every study is using a different dose and measuring a different end point.
Control groups, when they’re included, include a variety of other treatments that may obscure the results.
Very few groups are doing proper randomized placebo-controlled studies.
Nobody really knows the biochemical mechanism by which CQ and HCQ are supposed to work. The Yu et al. study points to an anti-inflammatory effect, while the Huang et al. study points to an effect on virus activation. There’s support in the literature for both possibilities.
Is anyone convinced yet why we need randomized placebo-controlled clinical trials? Why couldn’t these things have been tested before it became an emergency?
Here’s why. Treating infected patients is dangerous work. Studying the virus in the lab is even more dangerous, in more ways than one. A highly technical article on medium.com just came out describing how virus researchers have been introducing changes into viruses, usually but not always (he claims) creating non-pathogenic viruses. The goal is to identify features responsible for pathogenicity and to create knowledge essential for making vaccines. The author gives the impression of hubris in the field and claims, in contradiction to a number of reports in Nature and elsewhere, that the furin cleavage site in the SARS-CoV-2 DNA sequence looks out of place.
The researchers are being careful and working in BSL-4 containment. If the medium.com author is right, this suggests a potential failure of institutional oversight. I’m on one such committee (though not with viruses) and there’s definitely a certain amount of pressure to assume that an accident won’t happen and the safety protocol will be followed if it does. They also know, we hope, that making a mistake is not an option.
1. Huang M, Li M, Xiao F, Liang J, Pang P, Tang T, Liu S, Chen B, Shu J, You Y, Li Y, Tang M, Zhou J, Jiang G, Xiang J, Hong W, He S, Wang Z, Feng J, Lin C, Ye Y, Wu Z, Li Y, Zhong B, Sun R, Hong Z, Liu J, Chen H, Wang X, Li Z, Pei D, Tian L, Xia J, Jiang S, Zhong N, Shan H (2020) Preliminary evidence from a multicenter prospective observational study of the safety and efficacy of chloroquine for the treatment of COVID-19. MedrXiv preprint. doi: https://doi.org/10.1101/2020.04.26.20081059. Not yet certified by peer review
2. Yu, B., Wang, D. W., Li, C. (2020). Hydroxychloroquine application is associated with a decreased mortality in critically ill patients with COVID-19 https://www.medrxiv.org/content/10.1101/2020.04.27.20073379v1.full.pdf 10.1101/2020.04.27.20073379 Not yet certified by peer review
Hydroxychloroquine or gin and tonic. Gin and tonic, please and keep them coming.
I believe blood thinners are being trialled in NY.
https://www.nbcnews.com/health/health-news/blood-thinners-may-be-linked-reduced-covid-19-deaths-study-n1201276
A total of 395 were placed on ventilators. Among those who weren’t given a type of blood thinner called an anticoagulant, 62.7 percent died, compared with 29.1 percent of those who were given the medications.
You have not seen EVMS protocol
Anticoagulant is standard part of treatment
https://spectator.org/a-report-from-the-front/
Evms.edu/covidcare
I thought at least heparin was a standard medication for all severe ARDS patients? Why didn’t they do this? Or did they?
Might this be a reason why the death rate in Germany is so low (and shockingly as well around 30%…)?
Read this, it explains what is happening
Why there is aversion to anti coagulents…
https://spectator.org/a-report-from-the-front/
The EVMS protocol could improve survival rate but ~30% is already the rate for Germany so that might be as good as it gets.
CFR of closed cases for Germany still 5%. Undetected cases are guessed to be 4-8x more so estimated IFR would be 0.625-1.25% which is in the same ball park as the Lancet study.
There is no magic drug.
@Ron
Do you know, why these people recovered ?
Certainly you have no idea about, as everybody else, maybe you believe, all have been untreated 😀 – wishfull thinking 😀
Due to the shortage of PCR Virus tests for SARS-COV-2, hospitals in Ohio did not order the tests unless the patient was being admitted into the hospital for diagnosis (or had known exposure).
Consequently, hospital admission and treatment only occurred if the patient was already very ill.
So, even if you had flu-like symptoms with pulmonary symptoms (shortness of breath or difficulty taking a deep breath…which are uncommon with influenza) you would not get tested or hospitalized if your doctor thought you would recover on your own. My doctor made a provisional diagnosis of Covid-19 for my late March illness, but she did not order the PCR Virus test. I was advised to go to the ER if breathing got more difficult (improved but still recovering 6 weeks later).
I had asked about early HCQ treatment and was advised that Cleveland Clinic Foundation (CCF) doctors were “not encoutaged” to Rx Plaquenil for unapproved early Covid-19 treatment (I’m looking for a new doctor).
Certain that I had Covid-19, I sought a Serum Antibody Test (when Roche’s very accurate test became available last week). That request was also denied.
From the little information that’s available on HCQ studies…and just from common sense, HCQ therapies would be most effective when administered as early as possible…and with Zinc. The “tissue loading” aspect of Plaquenil would argue for having some on hand in case symptoms arise.
None of that matters because the Plaquenil is not available until you are hospitalized. Optimizing HCQ therapy is currently impossible…at least in the land of the CCF.
This is true in my state also. I could have a nurse come to my house with no prescription for HCQ, would have to be in hospital
I know why my Dr mentioned black market back in March
My new quest, aquire HCQ in any manner possible just to be sure I can find some if needed, it is difficult.
Anyone up for an outline on how to use dark web safely to buy hcq. Hate to take the trouble to do so, but what choice is there. Other ideas on how to aquire.
As always, read about EVMS protocol, https://spectator.org/a-report-from-the-front/
For those who are certain they know the ‘Truth’ about HCQ, I suggest reading the following:
https://www.wired.com/story/the-info-war-over-chloroquine-has-slowed-covid-19-science/?utm_source=twitter&utm_medium=social&utm_campaign=onsite-share&utm_brand=wired&utm_social-type=earned
Who started that info-war ?
Right, these media, with no other interest as to hunt Trump, and their lickspittles.
Clyde Spencer – (a ‘story’ in wired!!? srsly!!!??)
Paid mouthpiece for the opposition.
Change my mind.
If you don’t like Wired, how about Reuters? It is liberal, but doesn’t have any vested interest in taking Trump down.
https://www.reuters.com/article/us-health-coronavirus-hydroxychloroquine/malaria-drug-touted-by-trump-for-coronavirus-fails-another-test-idUSKBN22J3FP
The usual mo for the World Harvard Spin Network
1. Announce a bullshit study in the New England Journal of Medicine
2. There is not a chance the study will pass scrutiny. If you do not see that by now….
3. Affiliates of the WHSN spin the story around the world.
4. The FDA acts, almost sounds like they were scripted by guess who….
5. Big Pharma makes a bundle.
I have seen this before. Read something use full.
https://spectator.org/a-report-from-the-front/
For the straight stuff with no politics, can it be done..
https://www.evms.edu/media/evms_public/departments/internal_medicine/EVMS_Critical_Care_COVID-19_Protocol.pdf
Almost forgot..
From the WHSN, a tax exempt brokerage firm pretending to be a university
Here it wasn’t the question to take Trump down, but who started why the info-war, you see the difference ?
The media is intentionally ignoring the widespread use of HCQ+azithromycin + zinc by MDs in NYC . It has become the standard treatment for hospitalized cases and has been very effective. They don’t know or don’t want to know, and certainly don’t want the public to know.
Not across the board, I only hope it has changed
These original facebook and youtube were deleted
https://theconservativetreehouse.com/2020/04/26/an-alarming-message-about-healthcare-and-covid-19-in-new-york-city
And then is this catching on
https://spectator.org/a-report-from-the-front/